Metabolite levels such as the amount of urea and creatinine in blood are important disease indicators. Urea and creatinine levels are measured indirectly using enzyme-catalyzed hydrolysis to produce ammonium ions. Much work has focused on fabricating sensors for selective ammonium ion detection. In clinical use, the measurement of ammonium ion concentrations is achieved by carrier-based ion selective electrodes (ISEs) containing an ionophore, a ligand which has high selectivity and sensitivity to specific ions. The natural antibiotic nonactin is the most widely studied compound used as an ammonium ionophore. However, nonactin-based ammonium ISEs have a limit in their utility due to the poor selectivity of ammonium over potassium ions (log KNH4+,K+˜−0.9).
Modification of gold surfaces with self-assembled monolayers (SAMs) of organic compounds has received considerable interest due to the potential application of such as microfluidic sensors. The introduction of a selective ionophore in the adsorbates allows the development of rapidly responding chemical sensors. The use of SAMs in sensor technology has typically used electrochemical techniques to transduce the binding of the analyte. Cyclic voltammetry (CV) and impedance spectroscopy (IS) techniques allow the detection of metal cation complexation by the monolayer by measuring changes in conductivity or capacitance. There are reports in the literature of the preparation of SAMs of alkanethiols bearing crown-ethers that can complex non-electrochemically active ions such as Na+ and K+, or metallosalophenes that complex transition metal ions (e.g. Ni2+, Cu2+ and Co2+), whereby the binding processes were studied utilizing CV and impedance techniques. Also there are reports of the studies of ion recognition properties of other molecules on gold, such as helical peptides linked to a crown ether, crown ethers bonded to tetrathiafulvalene disulfides, and alkanethiols modified with nitrilotriacetic acid.
In our previous work an ammonium ionophore based on a cyclic depsi-peptide structure was incorporated into a planar ion-selective electrode (ISE) sensor format, which provides selectivity for NH4+ against the interfering ions, Na+, and K+, log KNH4+,Na+˜−2.1 and log KNH4+,K+˜−0.6. However the electrode require substantial amount of ionophore for fabrication and exhibits long equilibration times, which limits its practical applications.